Tetrahydro-1,5-benzoxazepines and tetrahydro-1H-1,5-benzodiazepines by a tandem reduction-reductive amination reaction

✍ Scribed by Richard A. Bunce; Christopher L. Smith; Jason R. Lewis

• Book ID: 102342938
• Publisher: Journal of Heterocyclic Chemistry
• Year: 2004
• Tongue: English
• Weight: 97 KB
• Volume: 41
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570410617

✦ Synopsis

Abstract

A tandem reduction‐reductive amination reaction has been applied to the synthesis of (±)‐4‐alkyl‐2,3,4,5‐tetrahydro‐1,5‐benzoxazepines and (±)‐4‐alkyl‐1‐benzoyl‐2,3,4,5‐tetrahydro‐1__H__‐1,5‐benzodiazepines. The nitro aldehydes and ketones required for 1,5‐benzoxazepine ring closures were prepared by nucleophilic aromatic substitution of the alkoxides from several 3‐buten‐1‐ol derivatives with 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Precursors for the 1,5‐benzodiazepines were prepared by similar addition of N‐(3‐butenyl)benzamide anions to 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Catalytic hydrogenation of the nitro carbonyl compounds using 5% palladium‐on‐carbon in methanol then gave the target heterocycles by a tandem reduction‐reductive amination sequence. The 1,5‐benzoxazepines were isolated in high yield following chromatographic purification; the 1,5‐benzodiazepines were isolated as solids directly from the hydrogenation mixture and possessed differentiated functionality on the two nitrogen atoms.